Various approaches of targeted therapies have been developed over the years. One approach has been to couple a drug or effector to a targeting agent such as an antibody. The antibody is used to change the distribution of drug or effector such that more of it can localize where it is most needed in vivo. Antibody-mediated cell depletion therapy has proven to provide significant clinical benefit in treatment of lymphomas and leukemia, driving the development of improved therapies with novel mechanisms of cell killing.
As an alternative to antibodies, nanoparticles that are targeted to single cell types have gained attention for their potential to provide selective delivery of therapeutic agents with reduced side effects. Liposomal nanoparticles are pharmaceutically proven delivery vehicles that can encapsulate a therapeutic agent and also display ligands that target cell-surface receptors. The challenge has been to identify a ligand that provides sufficient selectivity for the targeted cell. Certain high-affinity small-molecule ligands (e.g., folate) are efficient at targeting cognate receptors expressed at higher levels on the target cell, but lower expression levels on other cell types reduce selectivity. Immuno-liposomes use antibodies as targeting agents, but have not to date provided a therapeutic index commensurate with their promise.
There is a need in the art for better means for targeted delivery of therapeutic agents to single cell types in order to increase efficacy/potency and reduce side effect. The instant invention addresses this and other needs.